Ethylene-vinyl alcohol copolymer hollow fiber membranes and method of producing same

ABSTRACT

A hollow fiber membrane made of an ethylene-vinyl alcohol copolymer is provided, which is characterized in that, when observed in a dry state with an electron microscope, the hollow fiber membrane has at least one dense, active layer (or skin layer) on the inside and/or outside surface thereof and further a three-layered structure comprising two layers respectively contacting the inside and outside surfaces and each consisting of a plurality of particles bonded together and having particle sizes of 0.01 to 2 microns and a substantially particle-free homogeneous layer lying between the two layers. 
     A method of producing such hollow fiber membranes is also provided comprising spinning a spinning solution prepared by dissolving an ethylene-vinyl alcohol copolymer in a solvent mainly consisting of dimethyl sulfoxide, dimethylacetamide, pyrrolidone, N-methylpyrrolidone or a mixture of these through a spinneret for hollow fiber production while simultaneously introducing a coagulating liquid through the central aperture of said spinneret, passing the spun fiber through a gaseous atmosphere such that the fiber is drawn to 3 to 30 times its extrusion rate, and coagulating the fiber in a coagulation bath at a temperature within the range specified below: 
     When 15≦C≦40,  -15≦T≦1/4C+10 
     where C is polymer concentration (weight %) and T is coagulation temperature (°C.).

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to ethylene-vinyl alcohol (EVA) copolymer hollowfiber membranes and a method of producing the same. More particularly,it relates to novel EVA copolymer hollow fiber membranes presenting athree-layered structure comprising two layers consisting of bondedparticles and a homogeneous layer lying therebetween and at least oneactive or skin layer on the surface of said membrane, and to a method ofproducing the same.

2. Description of the Prior Art

Selectively-permeable membranes, especially hollow fiber membranes, arecoming into wide use in medical fields such as hemodialysis as well asin industrial fields such as in the ultrafiltration of varioussolutions.

EVA copolymer membranes which we have previously developed exhibitexcellent biocompatibility as well as membrane performancecharacteristics such as water permeability and permeability tosubstances having medium molecular weights. Consequently, the utility ofsuch membranes has been widely recognized in various fields.

Several EVA copolymer membranes have already been provided by thepresent inventors. Thus, U.S. Pat. No. 4,134,837, discloses an EVAcopolymer membrane having a structure comprising particles which haveparticle sizes of 100 to 10,000 Angstroms and which are bonded to eachother, said structure being recognizable throughout the membrane. Themembrane is excellent as a dialysis membrane in hemodialysis. Incopending U.S. patent application Ser. No. 962,962, filed Nov. 22, 1978,now U.S. Pat. No. 4,220,543, issued Sept. 2, 1980, there is disclosed ananisotropic membrane which is made of EVA copolymer compositions havingdifferent ethylene contents and contains cylindrical voids having alarge average length as well as spherical voids having sizes ranging upto 20 microns. Said membrane, too, is excellent as a dialysis membrane.Further, in copending U.S. patent application Ser. No. 06/71,671, nowU.S. Pat. No. 4,269,713, issued May 26, 1981, there is disclosed ananisotropic membrane which has a porous supporting layer containingvacuoles whose longitudinal lengths correspond to 20 to 99% of themembrane thickness. The membrane has a porosity of 60 to 90%. It isexcellent as a filtration membrane for ultrafiltration.

As is mentioned above, membranes with different structures can beproduced from EVA copolymers by varying production conditions.Therefore, EVA copolymers have been recognized as especially excellentmaterials for membranes.

As a result of further investigations, the present inventors havesucceeded in producing a novel EVA copolymer hollow fiber membrane whichis different in structure from those membranes described above.

SUMMARY OF THE INVENTION

Thus, the present invention provides an EVA copolymer hollow fibermembrane which is characterized in that, when observed in the dry statewith an electron microscope, the hollow fiber membrane has at least onedense and active layer (or a skin layer) on the inside and/or outsidesurfaces thereof and further a three-layered structure comprising twolayers respectively contacting the inside and outside surfaces and eachconsisting of a plurality of particles bonded together and havingparticle sizes of 0.01 to 2 microns and a substantially particle-freehomogeneous layer (referred to hereinafter as the "homogeneous layer")lying between said two layers.

The membrane according to the present invention is characterized in thatit has at least one active or skin layer on the membrane surface and athree-layered structure therebelow comprising two layers each consistingof particles bonded to each other and a homogeneous layer therebetween.

Known EVA copolymer membranes are divided generally into two classes. Inone class, the membrane has a substantially homogeneous structurethroughout the whole membrane. In the other, the membrane has ananisotropic structure comprising an active layer and a porous supportinglayer lying thereunder. To the contrary, however, the membrane of thepresent invention, in spite of its having an active layer, has no suchporous supporting layer thereunder as in the known membranes, but has athree-layered structure which comprises two layers consisting of aplurality of particles bonded together and a particle-free homogeneouslayer therebetween.

As will be described in more detail later, the hollow fiber membrane ofthe present invention exhibits excellent performance characteristicssuch as sharpness of cut off function. It is higher in permeability towater, to low-molecular-weight substances such as urea and tomedium-molecular-weight substances such as vitamin B₁₂ than theconventional EVA dialysis membranes, whereas it is highly effective inrejection of high-molecular-weight substances such as proteins anddextran. The correlation between such performance characteristics andthe membrane structure has not yet been elucidated. However, it isbelieved that the above-mentioned structure which is entirely differentfrom those of the conventional homogeneous EVA membranes is the verybasis for the excellent membrane characteristics of the presentinvention. The structure of the EVA copolymer membrane as disclosedherein is a novel one that has never been disclosed with respect tomembranes made of any materials including not only EVA polymers but alsoany other polymers.

The EVA copolymer to be used in this invention has an ethylene contentwithin the range of 10 to 90 mole %, preferably 10 to 60 mole % and aviscosity of 1.0 to 50 centipoises as measured in a 3 weight % solutionof EVA in dimethyl sulfoxide (DMSO) at 30° C. As will be described laterin more detail, the EVA polymer may be a copolymer containing othercopolymerizable monomer(s). Further, it may be crosslinked aftermembrane formation with such a crosslinking agent as an aldehydecontaining one or more aldehyde groups or a diisocyanate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an electron photomicrograph (magnification 3,600×) of anexample of the membrane according to the present invention.

FIG. 2 is a schematic representation of the membrane shown in thephotomicrograph of FIG. 1.

FIG. 3 is an electron photomicrograph (2,400×) of a hollow fibermembrane having the homogeneous structure as disclosed in U.S. Pat. No.4,134,837.

In FIG. 2, the membrane has an active layer (or skin layer) 1 on theoutside surface thereof. The layer 3 which is in contact with the activelayer 1 consists of a plurality of particles 2 bonded together. Theinside surface 5 may be either an active layer or a microporous layer.There is a layer 3' in contact with the inside surface. The layer 3'consists of a plurality of particles 2' bonded together. Between thelayers 3 and 3', there is a homogeneous layer 4, which does not presentany particle structure even in an electron photomicrograph taken at amagnification of 12,000 times. If the homogeneous layer 4 had a dense orcompact structure similar to that of the active layer, the membranewould not show such high permeability to water and solutes as mentionedabove. Therefore, it is believed that the homogeneous layer 4 has someother different structure from the conventional dense structure.However, the structure in question has not yet been completelyelucidated by the inventors. The layers 3 and 3' contain a large numberof particles having sizes within the range of 0.01 to 2 microns,preferably 0.05 to 1 micron, and are constructed such that thoseparticles which are close to the membrane surface have larger sizes andthe particle size decreases with the increase in distance from themembrane surface. Smaller particle sizes than those specified above willresult in unduly low permeability to water and solutes and thereforemake the membrane unsuited for the purpose of the invention. Structuresin which the particles have sizes above 2 microns cannot be produced bythe method of the present invention. The thicknesses of the particlelayers and the homogeneous layers can be varied on demand. When thethickness of the particle layer in contact with the outside surface isassumed to be 1, the thickness of the homogeneous layer is about 1 to15, preferably 2 to 8, and the thickness of the particle layer incontact with the inside surface is about 0.2 to 3, preferably 0.2 to 2.The active layer on the membrane surface is very thin. It does notreveal any micropores or gaps even under an electron microscope(magnification 12,000×). At least one of the outside and inside surfaceshas such an active layer. Without an active layer, membranecharacteristics are much inferior.

A hollow fiber membrane obtained according to the present invention hasan outside diameter of about 50 to 3,000 microns and a membranethickness of about 5 to 500 microns. The outside diameter and thethickness can be adjusted as required.

FIG. 3 is an electron photomicrograph (2,400×) of a hollow fibermembrane having the homogeneous structure as disclosed in U.S. Pat. No.4,134,837. The structure of the known homogeneous EVA membrane isclearly different from that of the membrane of the present invention.

In the present invention, the membrane structure can be examined in thefollowing manner. A dry membrane prepared by the process to be describedhereinbelow is frozen in liquid nitrogen and then broken to produce afracture. Gold is deposited on the fracture to a thickness of about 100Angstroms by a vapor phase deposition technique. Observation ofphotomicrography is performed by an electron microscope model HitachiHFS-2.

The present invention also provides a method of producing anethylene-vinyl alcohol copolymer hollow fiber membrane, which comprisesspinning a spinning solution prepared by dissolving an ethylene-vinylalcohol copolymer in a solvent selected from the group consisting ofdimethyl sulfoxide, dimethylacetamide, pyrrolidone, N-methylpyrrolidoneor a mixture thereof through a spinneret for hollow fiber productionwhile introducing a coagulating liquid through the central aperture ofsaid spinneret, passing the spun fiber through a gaseous atmosphere suchthat the fiber is drawn to 3 to 30 times its extrusion rate andsubsequently coagulating the fiber in a coagulation bath at atemperature within the range satisfying the following relationship;

When 15≦C≦40, -15 ≦T≦1/4C+10

where C is the polymer concentration (weight %) and T is the coagulationtemperature (°C.).

The EVA copolymer to be used in the practice of the present inventionmay be any of those mentioned previously. As mentioned above, it maycontain other copolymerizable comonomer(s) in an amount of not more than15 mole %. Suitable comonomers include methacrylic acid, vinyl chloride,methyl methacrylate, acrylonitrile, vinylpyrrolidone and the like. TheEVA copolymer may be crosslinked either before or after spinning bytreating the same with an inorganic crosslinking agent such as a boroncompound or an organic crosslinking agent such as a dissocyanate or adialdehyde. Further, the copolymer may be acetalized either before orafter spinning with an aldehyde such as formaldehyde, acetaldehyde,butyraldehyde or benzaldehyde to the extent of not more than 30 mole %of the functional hydroxyl groups in the vinyl alcohol units.

Whereas mono- and polyhydric alcohols such as methanol, ethanol,ethylene glycol and propylene glycol, phenol, m-cresol,methylpyrrolidone, formic acid and mixtures thereof with water are knownas solvents for dissolving EVA copolymers, it is preferable for theproduction of the membranes of the present invention to use dimethylsulfoxide, dimethylacetamide, pyrrolidone, N-methylpyrrolidone or amixture thereof. Especially preferred is dimethyl sulfoxide in which EVAcopolymers are highly soluble. The EVA copolymer can be dissolved in anyof the solvents mentioned above preferably at a concentration within therange of 15 to 40% by weight, more preferably 18 to 30% by weight. Thetemperature of the polymer solution is preferably 0° to 120° C., morepreferably 20° to 80° C. At higher temperatures, there is thepossibility of polymer deterioration. At lower temperatures, theviscosity of the solution becomes too high or gelation of the polymeroccurs, and in either case, spinning becomes difficult.

The spinning solution thus prepared is formed into a hollow fiber byextruding the solution through a spinneret for hollow fiber productionsuch as an annular nozzle. In practicing the invention, it is necessaryto introduce a coagulating liquid for the polymer solution through thecentral aperture of the spinneret during the spinning operation. Theliquid coagulant causes coagulation on the inside surface of the hollowfiber membrane, whereby the particle layer contacting the inside surfaceis formed. Optionally, an active layer can be made on the inside surfaceby appropriately selecting the coagulation conditons.

The liquid coagulant is, for example, water alone, a mixture of waterand a water-miscible organic solvent or an aqueous solution of a saltsuch as sodium sulfate. In the present invention, a mixture of water andthe same solvent as is used for the spinning solution with a watercontent of 40 to 70% by weight is especially preferred. The coagulatingability of said solution is especially suited for the formation of themembrane structure.

The spun fiber extruded through the spinneret first passes through agaseous atmosphere. Since the spun fiber remains fluid while in thegaseous atmosphere and while the spun fiber is drawn, a perfectly roundconfiguration with a uniform wall thickness is obtained. The fiber isalso subject to drawing in the gaseous atmosphere and coagulation in thecoagulation bath. It is totally unexpected that such a phenomenon canoccur in the production of hollow fiber membranes. In accordance withthe present invention, the draw ratio for the fiber is preferably 3 to30 times the extrusion rate and more preferably 5 to 20 times. Thedistance between the nozzle or spinneret and the surface of thecoagulation bath is preferably about 3 to 50 mm.

The gaseous atmosphere is usually an open air space. However, in caseevaporation of the polymer solution is to be controlled, it is possibleto arrange a covering member having a cylindrical or other appropriateshape so that an atmosphere may be provided which is filled with thevapor from the coagulation bath or with a separately supplied vapor orthrough which a controlled gas stream is passed.

The spun fiber is then led into the coagulation bath and coagulatedtherein. The composition and temperature of the coagulation bathrespectively may be selected over a broad range. However, it has beenfound desirable to use the same composition as that of theabove-mentioned coagulating liquid for introduction through the centralaperture of the spinneret. Thus, the aqueous solution of the solventused in preparing the spinning solution, especially an aqueous solutionof dimethyl sulfoxide, is preferred. The amount of each component shouldbe determined depending upon such conditions as the composition of thecoagulating liquid to be introduced through the central aperture of thespinneret and the coagulation temperature. Generally, the water contentis selected within the range of 20 to 80% by weight.

The coagulation temperature is also one of the important factorsinfluencing the formation of the membrane structure of the presentinvention. It has been found that the polymer concentration in thespinning solution and the temperature of the coagulation bath are eachrequired to be in a specified range. Namely, the following relationshipmust be satisfied:

When 15≦C≦40, -15≦T≦1/4C+10

where C is the polymer concentration (% by weight) and T is thecoagulation temperature (°C.).

The hollow fiber which has passed through the coagulation bath may befurther subjected to drawing between rollers, wet heat treatment, wetheat drawing and so on in order to adjust the membrane performance andmechanical properties. The fiber may also be acetalized in the vinylalcohol portions thereof with a monoaldehyde such as formaldehyde,acetaldehyde, chloroacetaldehyde or benzaldehyde or with a dialdehydesuch as glutaraldehyde, glyoxal or PVA dialdehyde, or further, there maybe introduced an ester crosslinkage with a diisocyanate such asphenylene diisocyanate or tolylene diisocyanate, or an ethercrosslinkage with epichlorohydrin, or other crosslinkages. Especiallypreferable is the crosslinking with a dialdehyde such as glutaraldehydebecause such crosslinking can improve heat durability, chemicalresistance, strength, dimensional stability, etc. to a large extent.

The hollow fiber membrane according to the invention can be used eitheras a wet membrane or as a dry membrane. Drying can be accomplished, forexample, by the method comprising replacing the water contained in thehollow fiber by a water miscible organic solvent incapable of dissolvingthe polymer, such as acetone, methanol or tetrahydrofuran, followed byremoving the organic solvent by mild heating, or the method comprisingtreating the fiber during or after the membrane formation with apolyhydric aliphatic alcohol such as ethylene glycol, diethylene glycolor glycerol, followed by drying by heating at a relatively lowtemperature, or the freeze-dry method comprising freezing the wetmembrane containing water in liquid nitrogen, for instance, followed byremoving the water by sublimation of the water under reduced pressure.

The hollow fiber membrane of the present invention can have a relativelysmall diameter and it can be used advantageously in an artificial kidneyor other medical uses because the priming volume can be reduced. It ishighly permeable to water and especially to low-molecular-weightsubstances such as urea and further is more highly effective inrejecting high-molecular-weight substances such as proteins than knownEVA membranes of homogeneous microstructure. Therefore, it is veryuseful as a membrane for hemodialysis or concentration of body fluidsuch as accumulated ascites.

The following examples further illustrate the inventions. Unlessotherwise specified, all percentages and parts are by weight.

EXAMPLES 1-6 AND COMPARATIVE EXAMPLE 1

An ethylene-vinyl alcohol copolymer with an ethylene content of 33 mole% was dissolved in dimethyl sulfoxide with heating to prepare a solutionwith a concentration of 22% by weight. The solution was allowed to standovernight to effect defoaming. An annular nozzle, 1.5 mm in nozzleopening diameter, 1.13 mm in outside diameter of the needle and 0.87 mm.in inside diameter of the needle, was arranged 20 mm. above thecoagulation bath. (In Examples 2-6, the parameters of the nozzle usedwere 0.96/0.6/0.31 mm.) While feeding through the inside portion of thenozzle a mixed solvent consisting of dimethyl sulfoxide and water in aratio of 45/55 wt/wt at a rate of 1.3 cc/min., the above defoamedspinning solution was extruded through the outer portion of the nozzleat a rate of 1.1 cc/min. into a coagulation bath containing a mixedsolution consisting of dimethyl sulfoxide and water. The spun fiber wasled vertically downward into the coagulation bath at a spinning rate of30 m/min. The wet hollow fiber thus produced showed an almost perfectlyround cross section with an outside diameter of 250 microns and amembrane thickness of 25 microns. Irregularities in diameter andmembrane thickness could hardly be observed over a fiber length of 1 km.Thus, the resulting fiber exhibited excellent uniformity. In comparativeExample 1, the fiber was directly led into the coagulation bath withoutpassing through the air atmosphere.

Table I summarizes the conditions employed and results obtained.

                                      TABLE I                                     __________________________________________________________________________                   Coag-         Hollow Fiber                                             Concentration                                                                        ulation                       Permeability                             (%) of DMSO                                                                          temper-                                                                            Draw                                                                              Rate of                                                                            Appearance (μ)                                                                             UFR                                      in coagulation                                                                       ature                                                                              Ratio                                                                             spinning                                                                           Outside                                                                            Inside                                                                             Membrane                                                                            (ml/cm.sup.2                                                                        Ureatidot.                                                                          VB.sub.12                    bath   (°C.)                                                                       X/1 (m/min.)                                                                           diameter                                                                           diameter                                                                           thickness                                                                           hr · atm)                                                                  (cm/min)                                                                            (cm/min.)            __________________________________________________________________________    Example                                                                             1 20     4    20.9                                                                              30   250  200  25    41 × 10.sup.-2                                                                360 × 10.sup.-4                                                               47 ×                                                                    10.sup.-4                  2 "      "    12.1                                                                              "    "    "    "     43    365   49                         3 "      "     4.0                                                                              10   440  360  43    69    380   55                         4 "      7    12.1                                                                              30   250  200  25    188   390   84                         5 60     4    "   "    "    "    "     39    350   46                         6 "      7    "   "    "    "    "     74    430   65                   Compara-                                                                      tive Ex-                                                                      ample 1 20     4     2.5                                                                               5   370  280  43    49    268   44                   __________________________________________________________________________

EXAMPLE 7 AND COMPARATIVE EXAMPLES 2 AND 3

The hollow fiber produced in Example 6 was fabricated into a module suchthat the membrane area amounted to 1.0 m², and the rejection rate of themodule for dextran of a molecular weight of 10,000 and the waterpermeability were determined under the conditions of a rate of bloodflow of 100 ml/min, with a blood pressure of 100 mmHg and a rate ofdialysate flow of 0 (zero). The dextran solution subjected to themeasurement had a concentration of 0.1% by weight. The rejection ratewas calculated by the following formula: ##EQU1##

In Comparative Example 2, the hollow fiber produced in ComparativeExample 1 was used for the same measurement. In Comparative Example 3, aregenerated cellulose hollow fiber membrane ["Cuprophan" trademark ofEnka Glanzstoff A. G.] with membrane thickness in the wet state of 30-35microns was used.

The results are shown in Table II.

                  TABLE II                                                        ______________________________________                                                               Rejection rate                                                     UFR        (%) for dextran                                                    (ml/hr · MMHg)                                                                  (M.W. 10,000)                                          ______________________________________                                        Example 7     6.7          55                                                 Comparative Example 2                                                                       4.3          49                                                 Comparative Example 3                                                                       2.9          75                                                 ______________________________________                                    

What is claimed is:
 1. An ethylene-vinyl alcohol hollow fiber membranewhich is characterized in that, when observed in the dry state with anelectron microscope, the hollow fiber membrane exhibits an annular crosssection having an outer surface and an inner surface, at least onesurface having a dense, active skin layer, said outer and inner surfacesseparated by a three-layered structure comprising two opposed layersrespectively contacting said outer and inner surfaces, said layers eachconsisting of a plurality of particles bonded together and havingparticle sizes ranging from 0.01 to 2 microns, and a substantiallyparticle-free homogeneous layer disposed therebetween.
 2. Anethylene-vinyl alcohol hollow fiber membrane as defined in claim 1having an ethylene content of from 10 to 90 mole % and a viscosity of1.0 to 50 centipoises as measured in a 3 weight % solution ofethylene-vinyl alcohol in dimethyl sulfoxide at 30° C.
 3. Anethylene-vinyl alcohol hollow fiber membrane as defined in claim 1wherein the particle size ranges from 0.05 to 1 micron.
 4. Anethylene-vinyl alcohol hollow fiber membrane as defined in claim 1wherein the relative thickness of the particulate layer in contact withthe outer surface to the particle-free homogeneous layer to theparticulate layer in contact with the inner surface ranges from 1:1 to15:0.2 to
 3. 5. An enthylene-vinyl alcohol hollow fiber membrane asdefined in claim 4 wherein the relative thicknessess range from 1:2 to8:0.2 to
 2. 6. An ethylene-vinyl alcohol hollow fiber membrane asdefined in claim 1 wherein the inner surface is a dense active skinlayer.
 7. An ethylene-vinyl alcohol hollow fiber membrane as defined inclaim 1 wherein the inner surface is a microporous layer.